PROJECT SUMMARY/ABSTRACT My long term goal is to independently investigate evidence-based therapeutics targeting the neurocognitive basis of affective disorders in youth. As a critical first step, the objectives of the research plan are to advance the development of interpretation bias training (IBT) to treat severe, chronic irritability in youth. Few evidence-based treatments exist for irritability, despite its impairing nature and long-lasting adverse effects. By establishing the targets of interpretation bias training, this treatment may be advanced towards efficacy trials. Whatever the outcome, this project will inform us of the neurocognitive basis of pathologic irritability, ultimately improving the mental health of irritable youth. My clinical interests led to an NIMH Clinical Fellowship to learn behavioral assessment and functional magnetic resonance imaging (fMRI) of youth with severe affective psychopathology. The Fellowship prepares trainees to seek independence via a K-series mechanism. Now, as an Assistant Professor at the University of Colorado (CU) School of Medicine, I have support to train to independence through a K23 mechanism. CU has resources at its medical and Boulder campuses necessary to pursue training in computational modeling, its application to neuroimaging, to further our understanding of pediatric mental illness. My mentorship team is led by Guido Frank, M.D. and includes experts in computational modeling and neuroimaging (Drs. Frank and Jones) as well as affective psychopathology and cognitive retraining trials (Drs. Leibenluft and Pine). My training plan provides the foundation for an independent research program. My training objectives are to: (1) train in the application and evaluation of cognitive retraining techniques to pediatric mental illness, (2) train in the development of computationally-intensive models describing brain-behavior interactions, (3) train in advanced neuroimaging and programming, (4) improve my research collaboration, writing, and presentation skills, (5) obtain additional training in the responsible conduct of research. I will accomplish these training objectives through coursework and other educational activities, guidance from my mentors/consultants, and completion of my research project. The research project proposed in this application is the first study to examine the neural and cognitive underpinnings of a recently developed IBT program to treat irritability transdiagnostically. It lays the foundation for a preliminary test of efficacy of IBT on irritability by establishing IBT's neurocognitive treatment targets: hostile interpretation bias and response in the neural threat-learning system. The design is a single-blinded, randomized controlled trial of IBT on its targets. We plan to apply established computational models to measure target response to IBT.